The expression of exogenous genes using Escherichia coli is a field on which a great many studies and developments of practical techniques have been made, and the field is one of the most advanced fields in molecular biology and genetic engineering. Nowadays, it has quite a high significance as a production process in industries, and a large number of biomedics have been industrially produced by a process using Escherichia coli. 
Escherichia coli strain which has been used most frequently in studies of molecular biology is a strain derived from K12 strain (Swartz, 1996, In Escherichia coli and Salmonella, Cellular and Molecular Biology, 2nd edition, ASM Press Washington, p.p. 1693-1711). In recent years, a strain derived from Escherichia coli B strain such as BL21 has been often used, and a list of strains which have been most frequently used for production of recombinant proteins has been presented by Wingfield, 1997 (Current Protocols in Protein Science, Coligan et al., Ed. John Wiley & Sons, Inc. 5.0.1-5.0.3).
A large number of systems in which proteins are expressed in bacterial hosts have been described in a document (Makrides, 1996, Microbiol. Rev. 60: 512-538; Current Opinions in Biotechnology, 1996, 7). An expression system comprises a promoter, its regulator, a ribosome immobilization site, a restriction site in whose downstream a useful gene can be introduced, a structure which can serve as a transcription terminator, a gene which is arbitrarily present in order to improve qualities of a super-expressed useful protein by simultaneous expression, and one or more vectors capable of introducing a combination of these into a host.
These vectors exist in cells in a predetermined copy number which is determined by interaction of two RNAs encoded by plasmids RNA I and RNA II (Polisky, 1988, Cell 55: 929-932). Regarding control of the copy number of expression plasmids in Escherichia coli, plural strategies have been described in documents (Swartz, 1996, In Escherichia coli and Salmonella, Cellular and Molecular Biology, 2nd edition, ASM Press Washington, p.p. 1693-1711, Makrides, 1996, Microbiol. Rev. 60: 512-538; Current Opinions in Biotechnology, 1996, 7).
When an exogenous gene is expressed by being incorporated into Escherichia coli, “compatibility” is required among an exogenous gene to be expressed, Escherichia coli and its gene expression system, and they are generally selected by a try-and-error method. Examples of cases where a desired protein is not obtained in a sufficient amount include a case in which a protein produced cannot obtain a normal structure inherent in the protein and becomes a precipitate (inclusion body) and a case in which a protein is decomposed immediately after produced. Many methods for solving such problems have been also introduced in documents (JP-A-10-313863, JP-A-8-140671, Makrides, 1996, Microbiol. Rev. 60, 512-538, Current Opinions in Biotechnology, 1996, 7).
As stated above, even with a lot of information and a huge number of expression systems and Escherichia coli strains, there are still a large number of genes which are hardly expressed stably, and in a great many cases where attempts to obtain proteins by expressing desired exogenous genes are made, proteins cannot be obtained in satisfactory quantities. Further, it is a phenomenon frequently observed that even purpose designed Escherichia coli strains are decreased in gene expression during storage or subculture, and what causes such a phenomenon is still unknown in many cases. For example, the present inventors invented a process for producing L-amino acids from various cinnamic acids using an amino group addition reaction of an enzyme ammonia lyase, and filed a patent application directed to the invention (JP-A-2003-225092). During the research process for the invention, a phenomenon that when Escherichia coli was transformed to express an enzyme ammonia lyase, activity of the transformant was decreased with each passage. This decrease in activity with passage is not attributed to methylation of an expression control site, plasmid loss, plasmid mutation and the like as generally mentioned as causes for decreased activity, and it cannot be avoided by any known information.
In case of basic studies in which the purpose can be attained by small-scale culture, problems are generally solved by conducting transformation again to obtain a new transformant. However, in case of relatively large-scale industrial production which involves multiple passages to take a long culture time, unstable gene expression is quite a serious problem.
However, among problems on stabilization of gene expression, those ever taken up and studied are only problems regarding prevention of loss of an exogenous gene due to loss of a plasmid and avoidance of deficient transcription due to modification or mutation of a plasmid. No measure against decrease in expression due to mutation of a host itself has ever been discussed. This is presumably because most of Escherichia coli strains used in laboratories as hosts are mutant strains modified to be held stably without mutation or modification of plasmids and there seems no information on further modification thereof. Moreover, the problems can be avoided by modification of exogenous genes including plasmids in some cases. Ordinarily, rather than mutation of host Escherichia coli strains, modification of exogenous genes as a proven method which has so far made some technical achievements has been attempted in many cases. However, modification of exogenous genes is a work which is time-consuming and laborious, and it is not always successful. In addition, there has been no approach to cope with expression of genes which cannot be stabilized even by modification of exogenous genes.